We propose to continue our HIV-1 acute infection and early disease research program (AIEDRP) that uses innovative approaches to recruit 60 or more subjects a year with acute/early HIV infection with high retention rates. Our overall objective is to understand the pathogenic steps in acute HIV infection and find therapeutic approaches to assure a favorable clinical course through enhancement of immune responses. Those subjects enrolled over the past 5 years and newly recruited subjects will constitute a cohort for longitudinal assessment of immunologic, virologic and clinical endpoints of HIV infection. Consenting subjects already on antiviral therapy will be participating in an ongoing STI trial. Other subjects will be randomized to receive combination antiviral treatment with or without IL-2 and with or without immunization with an HIV antigen. We will assess whether immune-based therapies enhance the ability of antiviral drug-treated individuals to maintain immunologic responses to HIV and keep the virus suppressed in blood and genital fluids after interruption of therapy. Subjects who have decided not to receive treatment will be followed and studied as observational controls. The findings should provide valuable information for the long-term control of HIV infection and transmission. Our Specific Objectives are the following: Determine the immunologic features that correlate with low viral load in blood and genital fluids, high CD4+ cell counts, and a healthy clinical state; Determine the optimal treatment approaches that will lead to a desirable immunologic and virologic set point for long-term control of HIV infection; Determine when a selected therapeutic strategy is stopped, which immunologic features prior to treatment interruption correlates with effective control of HIV infection. By investigating acute/early infection with the proposed in-depth virologic and immunologic studies, insights into the basic pathogenesis of HIV infection will be gained. The results should provide useful approaches for both industrialized and developing countries to improve the clinical outcome of infection and block HIV transmission.